System for inducing desirable temperature effects on body tissue

ABSTRACT

A catheter and catheter system may be used to treat disease tissue by gentle heating in combination with gentle or standard dilation. An elongate flexible catheter body with a radially expandable balloon having a plurality of electrodes engage tissue including diseased tissue when the structure expands.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of and claims the benefit of U.S.patent application Ser. No. 11/975,383 filed Oct. 18, 2007, which claimsthe benefit under 35 USC 119(e) of U.S. Provisional Application No.60/852,787, filed on Oct. 18, 2006, and entitled “Tuned RF Energy AndElectrical Tissue Characterization For Selective Treatment Of TargetTissues”; U.S. Provisional Application No. 60/921,973, filed on Apr. 4,2007, and entitled “Tuned RF Energy And Electrical TissueCharacterization For Selective Treatment Of Target Tissues”, and U.S.Provisional Application No. 60/976,733, filed on Oct. 1, 2007, entitled“System for Inducing Desirable Temperature Effects On Body Tissue”, thefull disclosures of which are incorporated herein by reference.

This application is related to U.S. patent application Ser. No.11/392,231, filed on Mar. 28, 2006, entitled “Tuned RF Energy forSelective Treatment of Atheroma and Other Target Tissues and/orStructures”; U.S. patent application Ser. No. 10/938,138, filed on Sep.10, 2004, and entitled “Selectable Eccentric Remodeling and/or Ablationof Atherosclerotic Material”; U.S. Patent Application No. 60/852,787,filed on Oct. 18, 2006, entitled “Tuned RF Energy And Electrical TissueCharacterization For Selective Treatment Of Target Tissues”; U.S.Provisional Application No. 60/921,973, filed on Apr. 4, 2007, entitled“Tuned RF Energy And Electrical Tissue Characterization For SelectiveTreatment Of Target Tissues”, and U.S. Provisional Application No.60/976,752, filed on Oct. 1, 2007, entitled “Inducing DesirableTemperature Effects on Body Tissue” the full disclosures of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention is generally related to medical devices, systems,and methods. In exemplary embodiments, the invention providescatheter-based treatment for luminal diseases, particularly foratherosclerotic plaque, vulnerable or “hot” plaque, and the like. Thestructures of the invention allow remodeling body tissue using heat.

Physicians use catheters to gain access to and repair interior tissuesof the body, particularly within the lumens of the body such as bloodvessels. For example, balloon angioplasty and other catheters often areused to open arteries that have been narrowed due to atheroscleroticdisease.

Balloon angioplasty is often effective at opening an occluded bloodvessel, but the trauma associated with balloon dilation can imposesignificant injury, so that the benefits of balloon dilation may belimited in time. Stents are commonly used to extend the beneficialopening of the blood vessel.

Stenting, in conjunction with balloon dilation, is often the preferredtreatment for atherosclerosis. In stenting, a collapsed metal frameworkis mounted on a balloon catheter which is introduced into the body. Thestent is manipulated into the site of occlusion and expanded in place bythe dilation of the underlying balloon. Stenting has gained widespreadacceptance, and produces generally acceptable results in many cases.Along with treatment of blood vessels (particularly the coronaryarteries), stents can also be used in treating many other tubularobstructions within the body, such as for treatment of reproductive,gastrointestinal, and pulmonary obstructions.

Restenosis or a subsequent narrowing of the body lumen after stentinghas occurred in a significant number of cases. More recently, drugcoated stents (such as Johnson and Johnson's Cypher™ stent, theassociated drug comprising Sirolimus™) have demonstrated a markedlyreduced restenosis rate, and others are developing and commercializingalternative drug eluting stents. In addition, work has also beeninitiated with systemic drug delivery (intravenous or oral) which mayalso improve the procedural angioplasty success rates.

While drug eluting stents appear to offer significant promise fortreatment of atherosclerosis in many patients, there remain many caseswhere stents either cannot be used or present significant disadvantages.Generally, stenting leaves an implant in the body. Such implants canpresent risks, including mechanical fatigue, corrosion, and the like,particularly when removal of the implant is difficult and involvesinvasive surgery. Stenting may have additional disadvantages fortreating diffuse artery disease, for treating bifurcations, for treatingareas of the body susceptible to crush, and for treating arteriessubject to torsion, elongation, and shortening.

A variety of modified restenosis treatments or restenosis-inhibitingocclusion treatment modalities have also been proposed, includingintravascular radiation, cryogenic treatments, ultrasound energy, andthe like, often in combination with balloon angioplasty and/or stenting.While these and different approaches show varying degrees of promise fordecreasing the subsequent degradation in blood flow followingangioplasty and stenting, the trauma initially imposed on the tissues byangioplasty remains problematic.

A number of alternatives to stenting and balloon angioplasty so as toopen stenosed arteries have also been proposed. For example, a widevariety of atherectomy devices and techniques have been disclosed andattempted. Despite the disadvantages and limitations of angioplasty andstenting, atherectomy has not gained the widespread use and successrates of dilation-based approaches. More recently, still furtherdisadvantages of dilation have come to light. These include theexistence of vulnerable plaque, which can rupture and release materialsthat may cause myocardial infarction or heart attack.

In light of the above, it would be advantageous to provide new devices,systems, and methods for remodeling of the lumens of the body, andparticularly of the blood vessels. It would further be desirable toavoid significant cost or complexity while providing structures whichcould remodel body lumens without having to resort to the trauma ofextreme dilation, and to allow the opening of blood vessels and otherbody lumens which are not suitable for stenting.

BRIEF SUMMARY OF THE INVENTION

The present invention generally provides improved devices, systems, andmethods for treating diseased and other target tissues, optionally fortreatment of diseases of body lumens. Embodiments of the invention allowheating the body lumens. By radially expanding a balloon withelectrodes, plaque, fibrous vulnerable or “hot” plaques, along withhealthy tissues are heated by the energized electrodes using RF energy,microwave energy, ultrasound energy, and/or the like.

In one embodiment, a system is disclosed for inducing desirabletemperature effects on body tissue disposed about a lumen. The systemincludes a catheter body having a proximal end and a distal end, with aradially expandable member on the distal end. The expandable member hasa low profile insertion configuration and a larger profileconfiguration. A plurality of electrodes are disposed about theexpandable member so as to define a plurality of tissue volumes(“remodeling zones”) when the expandable member is in the large profileconfiguration within the lumen. The electrodes are radially coupled withthe tissue, and energy intended to remodel the tissue (“tissueremodeling energy”) is transmitted between the electrodes and thetissue, the electrodes configured to inhibit vaporization along thelumen while the remodeling energy inhibits both acute and long-termocclusion of the lumen.

In another embodiment, a method for using a catheter system is disclosedfor inducing desirable temperature effects on desired body tissuedisposed about a lumen of a patient. The method includes positioning aradially expandable member supported by a distal end of a catheter bodywithin the lumen adjacent the desired tissue to be heated, theexpandable member having a low profile insertion configuration and alarger profile configuration. Expanding the expandable member to thelarger profile configuration within the lumen so as to engage aplurality of electrodes against the desired tissue, the plurality ofelectrodes defining a plurality of remodeling zones in the tissue.Energizing the plurality of electrodes with a controller having a powersource electrically coupled to the plurality of electrodes and heatingthe remodeling zones in the tissue with the energized electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1A illustrates diffuse atherosclerotic disease in which asubstantial length of multiple blood vessels has limited effectivediameters.

FIG. 1B illustrates vulnerable plaque within a blood vessel.

FIG. 1C illustrates the sharp bends or tortuosity of some blood vessels.

FIG. 1D illustrates atherosclerotic disease at a bifurcation.

FIG. 1E illustrates a lesion associated with atherosclerotic disease ofthe extremities.

FIG. 1F is an illustration of a stent fracture or corrosion.

FIG. 1G illustrates a dissection within a blood vessel.

FIG. 1H illustrates an artery wall around a healthy artery.

FIG. 1I illustrates a restenosed artery.

FIG. 2 schematically illustrates a balloon catheter system according tothe present invention.

FIG. 3 schematically illustrates one embodiment of an inflatable balloonfor use in the catheter system of FIG. 2.

FIGS. 4A and 4 show an exemplary balloon catheter supporting electrodesand an exemplary RF generator structure, respectively, for use in thesystems and methods described herein.

FIG. 5A schematically illustrates one embodiment of electrodes in acircumferential array mounting to a balloon.

FIGS. 5B and 5C schematically illustrates electrodes in flexiblecircuit/circuitry.

FIGS. 6A and 6B schematically illustrate one embodiment of electrodeshaving an electroplated balloon portion with an internal electrode base.

FIGS. 7A and 7B schematically illustrate one embodiment of ballooncatheter system for use for monopolar energy treatment.

FIGS. 8A-8D schematically illustrate placement of electrode pairs foruse in bipolar energy treatment.

FIGS. 9A-9C illustrate a method of using a balloon catheter systemtreating artery tissue.

FIG. 10 illustrates frequency targeting of tissues.

FIG. 11 illustrates various electrode energy settings to achievetemperatures between 50° C. and 65° C.

FIG. 12A schematically illustrates a mono-polar configuration.

FIG. 12B schematically illustrates a bipolar configuration.

FIG. 13 schematically illustrates electrodes arranged on a balloon in aradial topology.

FIG. 14 schematically illustrates electrodes arranged on a balloon in alongitudinal topology.

FIG. 15A schematically illustrates diseased tissue that is concentricabout the entire circumference of an artery.

FIG. 15B schematically illustrates diseased tissue that is eccentricabout a portion of an artery along with healthy tissue.

FIG. 16 graphically illustrates advantageous treatment power and timeranges for different electrode geometries, for use in embodiments of theinvention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides devices, systems, and methods to treatluminal tissue. The invention will be particularly useful for remodelingmaterials along a partially occluded artery in order to open the arterylumen and increase blood flow. The devices, systems, and methodsdisclosed herein may be used in any artery, for example, the femoral,popliteal, coronary and/or carotid arteries.

While the disclosure focuses on the use of the technology in thevasculature, the technology would also be useful for any luminalobstruction. Other anatomical structures in which the present inventionmay be used are the esophagus, the oral cavity, the nasopharyngealcavity, the auditory tube and tympanic cavity, the sinus of the brain,the arterial system, the venous system, the heart, the larynx, thetrachea, the bronchus, the stomach, the duodenum, the ileum, the colon,the rectum, the bladder, the ureter, the ejaculatory duct, the vasdeferens, the urethra, the uterine cavity, the vaginal canal, and thecervical canal.

Some embodiments of the vascular treatment devices, systems, and methodsdescribed herein may be used to treat atherosclerotic disease by gentleheating in combination with gentle or standard dilation. For example, anangioplasty balloon catheter structure having electrodes disposedthereon might apply electrical potentials to the vessel wall before,during, and/or after dilation, optionally in combination with dilationpressures which are at or significantly lower than standard, unheatedangioplasty dilation pressures. Where balloon inflation pressures of10-16 atmospheres may, for example, be appropriate for standardangioplasty dilation of a particular lesion, modified dilationtreatments combined with appropriate electrical potentials (throughflexible circuit electrodes on the balloon, electrodes depositeddirectly on the balloon structure, or the like) described herein mayemploy from 10-16 atmospheres or may be effected with pressures of 6atmospheres or less, and possibly as low as 1 to 2 atmospheres. Suchmoderate dilations pressures may (or may not) be combined with one ormore aspects of the tissue characterization, tuned energy, eccentrictreatments, and other treatment aspects described herein for treatmentof diseases of the peripheral vasculature.

In many embodiments, gentle heating energy added before, during, and orafter dilation of a blood vessel may increase dilation effectivenesswhile lowering complications. In some embodiments, such controlledheating with balloon may exhibit a reduction in recoil, providing atleast some of the benefits of a stent-like expansion without thedisadvantages of an implant. Benefits of the heating may be enhanced(and/or complications inhibited) by limiting heating of the adventitiallayer below a deleterious response threshold. In many cases, suchheating of the intima and/or media may be provided using heating timesof less than about 10 seconds, often being less than 3 (or even 2)seconds. In other cases, very low power may be used for longerdurations. Efficient coupling of the energy to the target tissue bymatching the driving potential of the circuit to the target tissue phaseangle may enhance desirable heating efficiency, effectively maximizingthe area under the electrical power curve. The matching of the phaseangle need not be absolute, and while complete phase matching to acharacterized target tissue may have benefits, alternative systems maypre-set appropriate potentials to substantially match typical targettissues; though the actual phase angles may not be matched precisely,heating localization within the target tissues may be significantlybetter than using a standard power form.

Remodeling may involve the application of energy, typically in the formof RF, microwave and/or ultrasound energy to electrodes, and the like.This energy will be controlled so as to limit a temperature of targetand/or collateral tissues, for example, limiting the heating of afibrous cap of a vulnerable plaque or the intimal layer of an arterystructure. In some embodiments, the surface temperature range is fromabout 50° C. to about 90° C. For gentle heating, the surface temperaturemay range from about 50° C. to about 65° C., while for more aggressiveheating, the surface temperature may range from about 65° C. to about90° C. Limiting heating of a lipid-rich pool of a vulnerable plaquesufficiently to induce melting of the lipid pool while inhibitingheating of other tissues (such as an intimal layer or fibrous cap) toless than a surface temperature in a range from about 50° C. to about65° C., such that the bulk tissue temperature remains mostly below 50°C.-55° C. may inhibit an immune response that might otherwise lead torestenosis, or the like. Relatively mild surface temperatures between50° C. and 65° C. may be sufficient to denature and break protein bondsduring treatment, immediately after treatment, and/or more than onehour, more than one day, more than one week, or even more than one monthafter the treatment through a healing response of the tissue to thetreatment so as to provide a bigger vessel lumen and improved bloodflow.

While the methods and devices described herein are not selective intissue treatment of the blood vessel, the devices can be used fortreatment of both concentric and eccentric atherosclerosis. This nonselective treatment is a particular advantage because atherosclerosismay be eccentric relative to an axis of the blood vessel over 50% of thetime, possibly in as much as (or even more than) 75% of cases.

Hence, remodeling of atherosclerotic materials may comprise shrinkage,melting, and the like of atherosclerotic and other plaques.Atherosclerotic material within the layers of an artery may bedenatured, melted and/or the treatment may involve a shrinking ofatherosclerotic materials within the artery layers so as to improveblood flow. The invention may also provide particular advantages fortreatment of vulnerable plaques or blood vessels in which vulnerableplaque is a concern, which may comprise eccentric lesions. The inventionwill also find applications for mild heating of the cap structure (toinduce thickening of the cap and make the plaque less vulnerable torupture) and/or heating of the lipid-rich pool of the vulnerable plaque(so as to remodel, denature, melt, shrink, and/or redistribute thelipid-rich pool).

While the present invention may be used in combination with stenting,the present invention is particularly well suited for increasing theopen diameter of blood vessels in which stenting is not a viable option.Potential applications include treatment of diffuse disease, in whichatherosclerosis is spread along a significant length of an artery ratherthan being localized in one area. The invention may also findadvantageous use for treatment of tortuous, sharply-curved vessels, asno stent need be advanced into or expanded within the sharp bends ofmany blood vessel. Still further advantageous applications includetreatment along bifurcations (where side branch blockage may be anissue) and in the peripheral extremities such as the legs, feet, andarms (where crushing and/or stent fracture failure may be problematic).

In some instances, it may be desirable to obtain baseline measurementsof the tissues to be treated (which may be characterized viaintravascular ultrasound, optical coherence tomography, or the like) maybe taken to help differentiate adjacent tissues, as the tissuesignatures and/or signature profiles may differ from person to person.Additionally, the tissue signatures and/or signature profile curves maybe normalized to facilitate identification of the relevant slopes,offsets, and the like between different tissues. Any of the techniquesdisclosed in U.S. Patent Application No. 60/852,787, entitled “Tuned RFEnergy And Electrical Tissue Characterization For Selective Treatment OfTarget Tissues”; and U.S. Provisional Application No. 60/921,973, filedon Apr. 4, 2007, entitled “Tuned RF Energy And Electrical TissueCharacterization For Selective Treatment Of Target Tissues”, the fulldisclosures of which are incorporated herein by reference, may becombined with the present invention.

Diffuse disease and vulnerable plaque are illustrated in FIGS. 1A and1B, respectively. FIG. 1C illustrates vascular tortuosity. FIG. 1Dillustrates atherosclerotic material at a bifurcation, while FIG. 1Eillustrates a lesion which can result from atherosclerotic disease ofthe extremities.

FIG. 1F illustrates a stent structural member fracture which may resultfrom corrosion and/or fatigue. Stents may, for example, be designed fora ten-year implant life. As the population of stent recipients liveslonger, it becomes increasingly likely that at least some of thesestents will remain implanted for times longer than their designed life.As with any metal in a corrosive body environment, material degradationmay occur. As the metal weakens from corrosion, the stent may fracture.As metal stents corrode, they may also generate foreign body reactionand byproducts which may irritate adjoining body tissue. Such scartissue may, for example, result in eventual reclosure or restenosis ofthe artery.

Arterial dissection and restenosis may be understood with reference toFIGS. 1G through 1I. The artery comprises three layers, an endotheliallayer, a medial layer, and an adventitial layer. During traditionalangioplasty, the inside layer may delaminate or detach partially fromthe wall so as to form a dissection as illustrated in FIG. 1G. Suchdissections divert and may obstruct blood flow. FIG. 1H illustrates anartery wall around a healthy artery and FIG. 1I illustrates a restenosedartery. As can be understood by comparing FIGS. 1H and 1I, traditionalangioplasty is a relatively aggressive procedure which may injure thetissue of the blood vessel. In response to this injury, in response tothe presence of a stent, and/or in the continuing progression of theoriginal atherosclerotic disease, the opened artery may restenose orsubsequently decrease in diameter as illustrated in FIG. 1I. While drugeluting stents have been shown to reduce restenosis, the efficacy ofthese new structures several years after implantation has not be fullystudied, and such drug eluting stents are not applicable in many bloodvessels.

In general, the present invention provides a catheter system which isrelatively quick and easy to use by the physician. The catheter systemof the present invention uses mild heat to provide tissue surfacetemperatures in a range between about 50° C. and 65° C. to gentlyremodel the tissue, that may allow arteries to be opened.

FIG. 2 shows one embodiment of a catheter system 10 for inducingdesirable temperature effects on artery tissue. The catheter system 10includes a balloon catheter 12 having a catheter body 14 with a proximalend 16 and a distal end 18. Catheter body 14 is flexible and defines acatheter axis 15, and may include one or more lumens, such as aguidewire lumen 22 and an inflation lumen 24 (see FIG. 3). Still furtherlumens may be provided if desired for other treatments or applications,such as perfusion, fluid delivery, imaging, or the like. Catheter 12includes an inflatable balloon 20 adjacent distal end 18 and a housing29 adjacent proximal end 16. Housing 29 includes a first connector 26 incommunication with guidewire lumen 22 and a second connector 28 in fluidcommunication with inflation lumen 24. Inflation lumen 24 extendsbetween balloon 20 and second connector 28. Both first and secondconnectors 26, 28 may optionally comprise a standard connector, such asa Luer-Loc™ connector. A distal tip may include an integral tip valve toallow passage of guidewires, and the like.

Housing 29 also accommodates an electrical connector 38. Connector 38includes a plurality of electrical connections, each electricallycoupled to electrodes 34 via conductors 36. This allows electrodes 34 tobe easily energized, the electrodes often being energized by acontroller 40 and power source 42, such as bipolar or monopolar RFenergy, microwave energy, ultrasound energy, or other suitable energysources. In one embodiment, electrical connector 38 is coupled to an RFgenerator via a controller 40, with controller 40 allowing energy to beselectively directed to electrodes 38. When monopolar RF energy isemployed, patient ground may (for example) be provided by an externalelectrode or an electrode on catheter body 14.

In some embodiments, controller 40 may include a processor or be coupledto a processor to control or record treatment. The processor willtypically comprise computer hardware and/or software, often includingone or more programmable processor unit running machine readable programinstructions or code for implementing some or all of one or more of themethods described herein. The code will often be embodied in a tangiblemedia such as a memory (optionally a read only memory, a random accessmemory, a non-volatile memory, or the like) and/or a recording media(such as a floppy disk, a hard drive, a CD, a DVD, a non-volatilesolid-state memory card, or the like). The code and/or associated dataand signals may also be transmitted to or from the processor via anetwork connection (such as a wireless network, an Ethernet, an interne,an intranet, or the like), and some or all of the code may also betransmitted between components of catheter system 10 and withinprocessor via one or more bus, and appropriate standard or proprietarycommunications cards, connectors, cables, and the like will often beincluded in the processor. Processor will often be configured to performthe calculations and signal transmission steps described herein at leastin part by programming the processor with the software code, which maybe written as a single program, a series of separate subroutines orrelated programs, or the like. The processor may comprise standard orproprietary digital and/or analog signal processing hardware, software,and/or firmware, and will typically have sufficient processing power toperform the calculations described herein during treatment of thepatient, the processor optionally comprising a personal computer, anotebook computer, a tablet computer, a proprietary processing unit, ora combination thereof. Standard or proprietary input devices (such as amouse, keyboard, touchscreen, joystick, etc.) and output devices (suchas a printer, speakers, display, etc.) associated with modern computersystems may also be included, and processors having a plurality ofprocessing units (or even separate computers) may be employed in a widerange of centralized or distributed data processing architectures.

Balloon 20 is illustrated in more detail in FIG. 3. Balloon 20 generallyincludes a proximal portion 30 coupled to inflation lumen 24 and adistal portion 32 coupled to guidewire lumen 22. Balloon 20 expandsradially when inflated with a fluid or a gas. In some embodiments, thefluid or gas may be non-conductive and/cooled. In some embodiments,balloon 20 may be a low pressure balloon pressurized to contact theartery tissue. In other embodiments, balloon 20 is an angioplastyballoon capable of higher pressure to both heat the artery tissue andexpand the artery lumen. Balloon 20 may comprise a compliant ornon-compliant balloon having helical folds to facilitate reconfiguringthe balloon from a radially expanded, inflated configuration to a lowprofile configuration, particularly for removal after use.

Electrodes 34 are mounted on a surface of balloon 20, with associatedconductors 36 extending proximally from the electrodes. Electrodes 34may be arranged in many different patterns or arrays on balloon 20. Thesystem may be used for monopolar or bipolar application of energy. Fordelivery of monopolar energy, a ground electrode is used, either on thecatheter shaft, or on the patients skin, such as a ground electrode pad.For delivery of bipolar energy, adjacent electrodes are axially offsetto allow bipolar energy to be directed between adjacent circumferential(axially offset) electrodes. In other embodiments, electrodes may bearranged in bands around the balloon to allow bipolar energy to bedirected between adjacent distal and proximal electrodes.

Referring now to FIG. 4A, an exemplary balloon catheter structure havingan array of electrodes thereon can be seen. FIG. 4B illustrates anexemplary RF generator for energizing the electrodes of the ballooncatheter of FIG. 4A. The balloon catheter and RF generator of FIGS. 4Aand 4B were used in a series of experiments on animal models, with theballoons having diameter sizes ranging from about 3 mm to about 8 mm.The test subjects comprised Healthy domestic swine and YucatanMini-Swine. Atherosclerotic disease was induced (Injury & HFHC diet), todemonstrate the ability of a system including the balloon catheter andRF generator of FIGS. 4A and 4B to deliver controlled therapy to arterywalls. Histology was obtained at post-treatment endpoints to determinethe extent of tissue damage and the appropriate treatment dose ranges.

Electrodes 34 may be mounted on balloon 20 using any suitableattachment. In the embodiment shown in FIG. 5A, electrodes 34 aremounted or made on a flexible substrate or “flexible circuit” 35 that isattached to the balloon 20 with a suitable adhesive. The associatedconductors 36 are attached to the catheter body 14. The flexible circuit35 should be flexible to allow folding and inflation of the balloon.Each flexible circuit 35 includes multiple pads 34, for example, apreferred embodiment includes sixteen pads arranged in a linear arrayelectrode.

Referring now to FIG. 5B, a flexible circuit panel 110 having flexiblecircuits 112, 114, and 116 is shown. Each of the flexible circuitsinclude electrically conductive leads 118 that extend between proximalelectrical contacts 120 and distal electrodes 122. Leads 118 aresupported by a flexible polymer substrate 124, and the flexible circuitsmay be used in catheter 12 (see FIG. 1), for example, by cutting thesubstrate around and/or between the electrical components of thecircuit, mounting the electrodes to balloon 20, and extending leads 118toward and/or along catheter body 14 for electrical coupling tocontroller or processor 40 and energy source 42. One or more flexiblecircuits may be mounted to balloon 20, with the electrodes of eachflexible circuit optionally providing a grouping or sub-array ofelectrodes for treating a plurality of remodeling zones in the targettissue. Alternative sub-arrays may be provided among electrodes ofdifferent flexible circuits, may be defined by programmable logic of theprocessor, and/or may comprise any of a wide variety of alternativeelectrode circuit structures, with the sub-arrays often being employedfor multiplexing or treating the region of target tissue with aplurality of differing electrical energy paths through the tissue.

Still referring to FIG. 5B, multiplexing between selected electrodes ofan array or sub-array can be effected by selectively energizingelectrode pairs, with the remodeling zones for the sub-array beingdisposed between the electrodes of the pairs so that the energy passestherethrough. For example, a pair of electrodes selected from electrodes1, 2, 3, 4, 5, and 6 of flexible circuit 112 (with the selectedelectrodes optionally being positioned opposite each other) may beenergized and then turned off, with another pair then being energized,and so forth. The firing order might be 1 and 4, then 2 and 5, then 3and 6. Bipolar potentials between the electrodes of the pair can inducecurrent paths in the same general tissue region, with the powerdissipated into the tissue optionally remaining substantially constant.This provides a duty cycle of about ⅓ with respect to heat and/or lossesat each electrode surface. The four electrode configurations of flexiblecircuits 114 and 116 could be used in a similar manner. Monopolar energymight also be applied using a larger ground pad on the skin of thepatient or the like.

FIG. 5C shows flexible circuit panels 128 having flexible circuits 35for use in FIG. 5A. Each of the flexible circuits 35 includeelectrically conductive leads 36 that extend between proximal electricalcontacts 132 and distal electrodes 34. In the embodiment shown, each legof flexible circuit 35 contains 16 electrodes 34 connected with onecontact 132. This minimized the number of wires needed for conductiveleads 36. The electrode pad may be 0.5 mm wide with 0.2 mm spacingbetween electrodes 34. The length and width of the electrode pad andnumber of electrodes may be changed for a desired impedance, forexample, to match the impedance of the controller or generator. Leads 36are supported by a flexible polymer substrate 134, and the flexiblecircuits may be used in catheter 12 (see FIG. 1), for example, bycutting the substrate around and/or between the electrical components ofthe circuit, mounting the electrodes to balloon 20, and extending leads36 toward and/or along catheter body 14 for electrical coupling tocontroller or processor 40 and energy source 42. One or more flexiblecircuits may be mounted to balloon 20, with the electrodes of eachflexible circuit optionally providing a grouping or sub-array ofelectrodes for treating a plurality of remodeling zones in the targettissue (See FIGS. 8A-8D). Alternative sub-arrays may be provided amongelectrodes of different flexible circuits, may be defined byprogrammable logic of the processor, and/or may comprise any of a widevariety of alternative electrode circuit structures, with the sub-arraysoften being employed for multiplexing or treating the region of targettissue with a plurality of differing electrical energy paths through thetissue.

In one embodiment, a solid insulated wire of suitable size is flattenedon a distal end, for example being coined or rolled, squashing the wireto create a shape appropriate for an electrode 34. The insulation alongthe coined surface is removed. In some embodiments, the wire is made ofplatinum, while in other embodiments, the coined surface iselectroplated with gold. The wire and electrode are then placed in thecorrect position and adhered to the balloon 20.

FIG. 6A shows one embodiment in which electroplated portions 50 of aballoon 20 act as the electrodes 34 with an electrode base 52 placed onthe inside of the balloon 20. In this embodiment, a portion of a balloonis electroplated so it may conduct electricity through its wall.Electroless plating or metal deposition may also be used. Thewire-electrode 52 is adhered to the inside of the balloon withconductive epoxy 54, the balloon becomes the surface of the electrode34. To minimize the current density within the wall of the balloon, thewire electrode may be in the same pattern as that electroplated on theballoon. The wire-electrodes may be manufactured from a wire 56 in aforging process similar to that used in the making of nails, shown inFIG. 6B. An end of a magnetic wire 56 is placed into a forging mold 58so that a length of wire, whose volume is equal to that of the desiredelectrode is extended into the mold and forged into the electrode base52. The wire-electrode, with the exception of the electrode base, may beinsulated, so that the electrodes are isolated from one another and fromthe fluid used for balloon inflation. This method will encapsulate theassembly, minimize the risk of electrode delamination, increase themanufacturing yield, and is adaptable to any desirable electrode shapeand patterning.

In another embodiment, electrodes 34 contain materials of differingspecific resistivity cured on the balloon 20. One example is using anexcimer laser to selectively cure photocurable ink on the balloon. Thus,electrode pads and traces may bye directly mounted on the balloon. Thisprocess starts by covering the balloon with photocurable orphotoimageable conductive ink. A laser is then used to direct write thetraces and electrode pads (UV cure) The uncured conductive ink is thenremoved or rinsed off. A cover layer is placed over the entire balloonand circuits, such as a parylene coating. The parylene coating is thenremoved to expose the electrode pads, for example, using an excimerlaser. The electrode pads are then coated with a conductive material,such as Ni/Au. In another embodiment, a direct drive laser printer isused to lay down a conductive ink circuit with electrode pads and traceson the balloon surface.

In some embodiments, small holes may be used to perfuse a fluid on ornear the electrodes to eliminate sticking of the electrodes to theartery tissue. The holes may be less than 1 μm in diameter and may bemade with a laser or ion beam. The holes may be made in the electrodes,flexible circuit, and/or balloon. In one example, electrode pads on aflexible circuit are designed with vias that are plated. The flexiblecircuit is mounted on a balloon and a laser or ion beam is used tocreate the holes in the flexible substrate and balloon. There may beseveral holes in the flexible/balloon for every electrode pad. Theballoon may then be perfused with standard perfusion balloon equipmentor specialized equipment. The perfusion approach may also provideadditional advantages beyond eliminating sticking, such as carrying awayheat or regulating impedance of the load.

In some embodiments if may be advantageous to embed electrodes 34 intothe artery tissue. The electrodes may have features to assist inimbedding, such as sharpened edges, needle protrusions, or the like,capable of piercing the artery tissue. For example, in a diseased tissuethere will be some fibrous surface tissue surrounding the lumen that maytend to conduct energy, thereby avoiding the diseased tissue. Thisfibrous surface may tend to dominate any impedance measurement if theyare probed superficially. By digging the electrodes into the wall of thefibrous cap, it may be possible to direct energy through the fibroustissue directly into the diseased tissue, or closer to the diseasedtissue. The energy may be Joule heating or a current source that putsmore heating into the diseased tissue with higher resistively. Thehealthy tissue can dissipate the energy without significant damage. Thistechnique may also assist in detecting diseased tissue electrically.

Monitoring the space between electrodes or electrode flexible circuitsduring inflation may assist in determining the direction of diseasedtissue within an artery. The space between pairs of electrodes increaseswith pressure in an elastic balloon when it is unconstrained duringinflation. When a balloon is placed within an eccentrically effecteddiseased tissue, the diseased portion stretches less than the healthytissue. So the change in the distance between the pairs changes more inthe healthy tissue and less in the diseased tissue, indicating thedirection, and maybe the amount, of diseased tissue in the artery.

Monopolar Treatment

FIG. 7A shows one embodiment of balloon catheter system for use formonopolar treatment of diseased tissue in a leg. A balloon catheter 20having electrodes 34 are positioned within an artery lumen 60 havingdiseased tissue 62. An electrical ground 64 is positioned on thepatients skin, or may be many ground electrode pads 68 positioned arounda patients leg 66, such a in a band or sock. When power is applied tothe multiple monopolar electrodes 34 arranged around the circumferenceof the artery lumen, energy 70 is directed radially outward through theartery wall.

By driving energy 70 radially outward, it is possible to force energythrough the disease tissue 62, which has a higher electrical resistivitythan healthy tissue. By applying low power for a long time duration, thedisease tissue may be treated. Low power is defined as the level ofpower which healthy tissue can dissipate the heat in a steady statewithout the healthy tissue temperature rising above a given threshold.The temperature may be between 45° C. and 50° C., which will denaturethe actin and myosin proteins that enable elastic recoil, withoutcausing excessive necrosis. The energy may be applied for a long time,where long is defined by the desired duration of the procedure, boundedon the high side by the amount of time healthy tissue can withstand theelevated temperature being caused, and bounded on the low side by theamount of time the diseased tissue needs for treatment to be complete.By treating for a long time, it is possible to accumulate heat in thediseased tissue, which has a lower heat capacity per mass and a lowerthermal conductivity. Variability in impedance can be compensated by thecontroller, in order to apply either constant power, constant current,or constant voltage, whichever has the most advantage.

The energy in the monopolar treatment shown if FIG. 7A travels outwardlyfrom the electrodes 34 and treats both diseased 62 and healthy arterytissue. Looking at the current path in tissue, diseased artery tissue,such as fat or lipidic material, has a low electrical conductivitycompared to other artery constituents. If this is true, the current 70may go around the diseased tissue 62 if possible, and find a lessrestrictive path, such as shown in FIG. 7B.

In some embodiments, internal 34 and external electrodes 68 may be usedto map artery plaque. By assembling a matrix of impedance readings, bothbipolar and monopolar, it may be possible to map the constituentcomposition and location of the disease in the artery. Once thisinformation in known, it may be possible to treat using the same knownelectrode positions. The treatment can either by monopolar or bipolar.Analysis is done weighting the contributions of the distance between theinternal and external electrodes with the contribution differences incellular composition in each path. Design of the external electrodes 68may be guided by computational capacity, maximizing the number ofelectrode points both around the circumference and along the patientsleg (lengthwise). In one embodiment, the external electrodes 68 areembedded in a sock or sleeve forming a matrix of electrodes on theoutside of the patients skin. This may device gives improved resolutionin measuring current paths from multiple directions and provides a wayto identify what the internal electrodes are opposed to in the artery.

Bipolar Treatment

FIGS. 8A-8D show different embodiments of electrodes 34 mountedcircumferentially on balloon 20 to provide treatment to artery tissueusing bipolar energy between electrode pairs 34A and 34B. The electrodepairs may be any electrode pairs on the balloon, for example, in someembodiments, the electrode pairs may be 34A and 34C, or 34A and 34D, or34A and 34E, or any combination of 34A-34E. This arrangement creates anenergy path through the tissue that delivers heat or energy inparticular treatment zones or segments 72 to the artery tissue betweenthe electrode pairs (“remodeling zones”). Using different combinationsof electrode pairs may reduce or eliminate gaps between the remodelingzones by using overlapping pairs. Using electrode pairs with bipolarenergy may avoid some potential issues of the monopolar approach.Diseased artery tissue has a higher electrical resistively than healthyartery tissue. If all the electrodes are energized, such as in amonopolar system, the heat or energy may flow through the healthy arterytissue and not into the diseased artery tissue (see FIG. 7B). By usingpairs of electrodes in a bipolar system, the heat or energy will gothrough the healthy tissue, diseased tissue, or a combination of bothhealthy and diseased tissues between the electrode pairs in theremodeling zones. Any number of electrode pairs may be used in differentpatterns or arrays. In the embodiments shown, the pitch betweenelectrode pairs remains the same, for example 3.14 mm, so that thetreatment volume is the same regardless of balloon size and each of theelectrode pairs use the same energy. As the balloons become larger, moreelectrode pairs are placed on the balloon, such as shown in FIGS. 8A-8D.The spacing between electrode pairs may range from about 0.25 to 2.5 mm,depending on balloon size. The maximum distance (angle) betweenelectrode pairs is 180 degrees on the balloon. FIG. 8A shows a balloonhaving a 3.0 mm diameter with three electrode pair in three segments72A. FIG. 8B shows a balloon having a 4.0 mm diameter with fourelectrode pair in four segments 72B. FIG. 8C shows a balloon having a5.0 mm diameter with five electrode pair in five segments 72C. FIG. 8Dshows a balloon having a 6.0 mm diameter with six electrode pair in sixsegments 72D.

The use of catheter system 10 for remodeling artery tissue by heatingcan be understood with reference to FIGS. 9A-9C. As seen in FIG. 9A,accessing of a treatment site will often involve advancing a guidewire74 within a blood vessel 76 at a target region of diseased tissue, suchas atherosclerotic material 78. Location of balloon 20 may befacilitated by radiopaque markers or by radiopaque structure (orcorresponding radiopaque markers placed on or near) balloon 20, and/orby the use of radiopaque electrodes 34. A wide variety of guidewires maybe used. For accessing a vessel having a total occlusion, guidewire 74may comprise any commercially available guidewire suitable for crossingsuch a total occlusion, including the Safe-Cross™ RF system guidewirehaving forward-looking optical coherence reflectometry and RF ablation.Where atherosclerotic material does not result in total occlusion of thelumen, such capabilities need not be provided in guidewire 74, althoughother advantageous features may be provided. Guidewire 74 may bepositioned under fluoroscopic (or other) imaging.

Catheter 12 is advanced distally over guidewire 74 and positionedadjacent to atherosclerotic material 62. Balloon 20 expands radiallywithin the lumen of the blood vessel so that electrodes 34 radiallyengage atherosclerotic material 78. As atherosclerotic material 78 maybe distributed eccentrically about catheter 12, some of electrodes 34may engage both atherosclerotic material 78 and healthy tissue 80, ascan be understood with reference to FIGS. 9B and 9C.

In some cases, an imaging may be used for identification and/orcharacterization of atherosclerotic materials, plaques, tissues,lesions, and the like from within a blood vessel. Suitable imagingcatheters for use in the present catheter system are commerciallyavailable from a wide variety of manufacturers. Suitable technologyand/or catheters may, for example, be commercially available from SciMedLife Systems and Jomed-Volcano Therapeutics (providers of intravascularultrasound catheters), Light Lab™ Imaging (developing andcommercializing optical coherence tomography catheters for intravascularimaging), Medtronic CardioRhythm, and the like. Still furtheralternative technologies may be used, including ultra fast magneticresonance imaging (MRI), electrical impedance atheroma depthmeasurements, optical coherence reflectometry, and the like.Non-invasive imaging modalities which may be employed include X-ray orfluoroscopy systems, MRI systems, external ultrasound transducers, andthe like. Optionally, external and/or intravascular atheroscleroticmaterial detectors may also be used to provide temperature information.For example, a system having an MRI antenna may detect tissuetemperatures such that a graphical indication of treatment penetrationmay be presented on the system display. Tissue temperature informationmay also be available from ultrasound and/or optical coherencetomography systems, and the temperature information may be used asfeedback for directing ongoing treatments, for selecting tissues fortreatment (for example, by identifying a hot or vulnerable plaque), andthe like.

As discussed above, electrodes 34 are positioned circumferentiallyaround the balloon 20. RF energy is directed to electrodes adjacentpairs of electrodes 34A and 34B, treating both atherosclerotic material78 and the healthy tissue 80. The controller 40 may energize theelectrodes with about 0.25 to 5 Watts average power for 1 to 180seconds, or with about 4 to 45 Joules. Higher energy treatments are doneat lower powers and longer durations, such as 0.5 Watts for 90 secondsor 0.25 Watts for 180 seconds. Most treatments in the 2 to 4 Watt rangeare performed in 1 to 4 seconds. Using a wider electrode spacing, itwould be appropriate to scale up the power and duration of thetreatment, in which case the average power could be higher than 5 Watts,and the total energy could exceed 45 Joules. Likewise, using a shorteror smaller electrode pair would require scaling the average power down,and the total energy could be less than 4 Joules. The power and durationare calibrated to be less than enough to cause severe damage, andparticularly less than enough to ablate diseased tissue 48 within ablood vessel. The mechanisms of ablating atherosclerotic material withina blood vessel have been well described, including by Slager et al. inan article entitled, “Vaporization of Atherosclerotic Plaque by SparkErosion” in J. of Amer. Cardiol. (June, 1985), on pp. 1382-6; and byStephen M. Fry in “Thermal and Disruptive Angioplasty: a Physician'sGuide;” Strategic Business Development, Inc., (1990) the fulldisclosures of which are incorporated herein by reference.

Referring now to FIG. 7C, as described above, balloon 20 may be anangioplasty balloon that combines heating with opening the artery lumen.In some embodiments, injury caused to the atherosclerotic material withthe energized electrodes or other energy directing surfaces may resultin subsequent resorption of the injured tissue lesions so as to providefurther opening of the vessel after termination of treatment as part ofthe healing process.

In some embodiments, balloon 20 may be repeatedly contracted, axialmovement of the catheter 12 employed to reposition balloon 20, withsubsequent expansion of balloon 20 at each of a plurality of treatmentlocations along atherosclerotic material 78.

The exemplary catheter devices and methods for their use describedherein are intended for application in the lumen of vessels of the humananatomy. The anatomical structure into which the catheter is placed maybe, for example, the esophagus, the oral cavity, the nasopharyngealcavity, the auditory tube and tympanic cavity, the sinus of the brain,the arterial system, the venous system, the heart, the larynx, thetrachea, the bronchus, the stomach, the duodenum, the ileum, the colon,the rectum, the bladder, the ureter, the ejaculatory duct, the vasdeferens, the urethra, the uterine cavity, the vaginal canal, and thecervical canal.

Frequency targeting of tissues is illustrated in FIG. 10. Differenttissue types have different characteristic electrical impedances thatcause the tissue to absorb energy of certain frequencies or frequencyranges more readily than others. By applying energy at the specificfrequency or range of frequencies that the tissue is more conductive,energy penetrates the tissue more readily. In general, it has been shownthat samples of diseased tissue exhibit higher impedance characteristicsthan samples of healthy tissue. In the case where a diseased area oftissue 78 is surrounded by relatively healthy tissue 80, the healthytissue is likely to shield the diseased tissue from electrical currentflow due to the lower impedance of the healthy tissue. Hence, minimal(or less than the desired) current flow 82 may pass through diseasedtissue 78, and heavier current flow 84 may be seen in low impedancehealthy tissue 80 when bipolar current is transmitted between electrodes34A and 34B. Typically, the frequency ranges in which tissue impedancevaries to a useful degree occur between 30 kilohertz and 30 Megahertz.

Frequency targeting seeks to deliver more energy to the diseased tissueby determining the frequency or range of frequencies at which theimpedance of the diseased tissue is equal to or less than that of thehealthy tissue, such as by operation at or above a threshold frequency.Energy delivered at the specified frequency or range of frequencies willcause more heat to be dissipated in the diseased tissue than energydelivered outside of those specific frequencies.

FIG. 11 shows some results of testing done on a cadaver aorta. By usingan average power between 1 and 5 Watts for between 0.5 and 10 secondsthe surface temperature reached was between 50 and 65° C. Sample dosesare shown below in Table 1

TABLE 1 Power Time Temp 1 Watt 8 sec 50° C. 2 Watts 2 sec 50° C. 3 Watts1.3 sec   50° C. 4 Watts 1 sec 50° C. 5 Watts .5 sec  50° C. 2 Watts 4sec 60° C. 3 Watts 2 sec 60° C. 4 Watts 1.5 sec   60° C. 5 Watts 1 sec60° C. 3 Watts 3 sec 65° C. 4 Watts 2 sec 65° C.

As the energies and powers for characterizing and/or treating tissuesare relatively low, the power source may optionally make use of energystored in a battery, with the power source and/or associated controlleroptionally being contained within a hand-held housing. Use of suchbattery-powered systems may have benefits within crowded operatingrooms, and may also help avoid inadvertent over treatment. The batteriesmay be disposable structures suitable to be included in a kit with asingle-use catheter, while the processor circuitry may be re-useable. Inother embodiments, the batteries may be rechargeable.

Electrode Design Considerations

Delivering RF energy directly to a specimen requires a conductive pathto be formed between two terminals or poles of an energy source.Currently there are two polar configurations that exist which satisfythis condition: a mono-polar configuration (FIG. 12A) and a bipolarconfiguration (FIG. 12B). In a mono-polar configuration there is asingle pole or electrode from which the energy emanates and a groundingplate or pad to absorb the energy and complete the circuit. Thisconfiguration creates higher energy densities at the electrode than atthe grounding pad which results in a single effected area or treatmentzone at the electrode which is directly related to the geometry of theelectrode and the power applied to the electrode. As the surface area ofthe mono-polar electrode increases, so does the size of the treatmentzone. The bi-polar configuration, on the other hand uses two poles orelectrodes to set up an electric field between the electrodes thuscreating a conduction path for the current to flow. Unlike themono-polar electrode configuration where only one geometric entity,surface area is deterministic to the treatment zone, the bi-polarelectrode configuration has three, electrode separation, parallel lengthand width, each of which have a separate and distinct effect on thetreatment zone.

If we take into consideration the effect each geometric entity has onthe effected treatment zone and the overall impedance as seen by thegenerator, we find that the separation or distance between electrodeshas the greatest effect, followed by parallel length and lastlyelectrode width. Electrode separation is governed by Coulombs law whichstates that the force between two charged objects is inverselyproportional to the square of the distance between them. In other wordsat very close distances the impedance as seen by a generator is verysmall and as we separate the electrodes the impedance increases at arate that is proportional to the square of their separation. As thisseparation increases, a higher potential energy is generated due to theincrease in impedance creating a greater flux density which results in agreater treatment depth. The effect of increasing the parallel lengthshared by the two electrodes causes the treatment zone to increase onlyas much as the parallel electrode length is increased. There are noadditional depth effects only an increase due to added length. Thisadditional length causes the impedance as seen by the generator todecrease due to the increase in potential parallel paths for the currentto flow through. Electrode width has the least effect on the treatmentzone and is governed by the same laws as electrode separation. As thewidth of the electrode is increased incrementally, the added effect issmall due to the inverse square law for each incremental element placedon the outer edges of the existing electrode elements. Although thiseffect may be small it aides in reducing the surface heat generated byreducing the current density at the inside edge of the electrode pairs.This effect is amplified as the conductance of the electrode materialapproaches the conductance of the tissue being treated due to the pathof least resistance becoming the tissue rather than the electrodeitself.

In order to better control the flow of electrical current to the insideof the arterial wall and to have a therapy which has the capability toselectively treat a desired area of an artery, the bipolar configurationis clearly the most desirable method of implementation.

Implementation requires that the electrodes be in contact with the innersurface of the arterial wall so the conductive path is the artery itselfand not the more conductive blood flowing within the artery. Manymechanism may be used to contact the electrodes to the inner surface ofthe arterial wall. In the present case, a balloon is used as thedeployment mechanism. The bipolar electrodes may be arranged on theballoon either a radial topology (FIG. 13) or a longitudinal topology(FIG. 14).

Each topology, radial and longitudinal, provides for a bi-polarconfiguration as well as offer a selective therapy, however the methodof selectivity of each topology differ. The radial topology offerslongitudinal selectivity along the length of an artery while thelongitudinal topology offers circumferential selectivity. When we thentake into consideration how atherosclerosis forms within an artery, wefind that it starts out at a localized area on the arterial wall andspreads along the wall sometimes completely occluding the flow of blood.In the case of complete occlusion or stenosis where the diseased tissueis concentric about the entire circumference of the artery (FIG. 15A),each topology will suffice. However, in the case where the diseasedtissue is eccentric and a portion of the artery is still healthy tissue(FIG. 15B), the longitudinal topology is preferred due to the differencein thermal and electrical conductivity between the healthy tissue anddiseased tissue. This difference, in the case of the radial topologywill cause the healthy portion to be treated more than the disease whichis not a desirable outcome. When we also take into consideration thatthe balloon must first be folded to reduce the cross sectional area fordeployment, it becomes clear that the longitudinal topology appears tobe the better choice.

The next was how to arrange the electrode on the balloon. How longshould the electrodes be? How wide should the electrodes be? And how farapart should the electrodes be separated? An initial starting point wasto use four balloon diameters, 3 mm, 4 mm, 5 mm and 6 mm. An electrodegeometry configuration was designed so that each balloon diameter wouldbe capable of accepting the same electrode geometry configurations, sono matter what size balloon was being used, the treatment could be thesame. With this configuration, the basic relationship of thecircumference of the balloon is related to the diameter by the factor ofπ (pi). The circumference of the balloon is equal to its diametermultiplied by π (pi). Using the balloon diameters to dictate the numberof electrode pairs placed on a balloon, the center to center electrodespacing would be π (pi) divided by 2. This configuration allows for theeven distribution of electrodes about the circumference of the balloonfor each whole number balloon diameter. With the electrodes center tocenter spacing decided, next is to figure out the ratio of theelectrodes width to their separation. This ratio would have to take into consideration the desired depth of treatment, as well as the effectsof surface heating. Taking these factors into consideration, a ratio ofapproximately 1:2 was selected. The actual numbers used were anelectrode width of 0.5 mm with a spacing of 1.07 mm, which fits nicelywith the π/2 center to center separation. This selected configurationalso allowed twice the number of possible treatment zones for eachballoon diameter (2n) as compared to one electrode pair for eachmillimeter of balloon diameter. Having twice the number of availabletreatment zones also meant that there was a greater potential forselectivity.

The last geometric entity yet to be decided was the length of theelectrodes. When trying to measure the impedance of the tissue theelectrodes are in contact with, it is more desirable to implementshorter electrodes so there is more sensitivity in the measurement andalso more immunity to noise. Shorter electrodes on the other hand alsomean that to treat an adequate area there needs to be many moreelectrode pairs and as a result more wires connecting those electrodesto the generator which will ultimately decrease the flexibility andcomplexity of the catheter. If long electrodes are used to reduce thewire count and to increase the potential treatment area, a different setof problems arise. Although long electrodes allow for a potentiallylarger treatment zone, they also allow for the possibility ofoverlapping into a healthy area which would result in an uneventreatment which could preferentially treat the healthy area rather thanthe diseased. The other disadvantage is the reduced sensitivity whenmeasuring impedance due to the increase in available current paths whichalso results in the need for larger diameter wires to accommodate theincreased current requirements. In solving this problem availableballoon lengths were looked at and 16 mm electrodes were chosen to useon a 20 mm balloon. This selection allowed for reasonable sensitivitywhile keeping the wire size to a minimum.

There are many available methods for placing electrodes onto a balloon,ranging from vapor deposition to flexible circuitry to individualmachined electrode and flattened wire. The main consideration was aproven manufacturing method, materials that could be placed in the bodyand parts that could be handled fairly easily without damage. Takingthese factors into consideration, the use of flexible circuitry waschosen as the method to manufacture the electrodes. Flexible circuitrymet all of the above criteria while still being flexible after beingmounted to the balloon. When designing the flexible electrodes, thedesign should ensure that the electrodes are in firm contact with thearterial wall, evacuating as much of the blood as possible. To achievethis, individual rounded pads were selected that were 0.5 mm wide by 0.8mm long separated by a distance of 0.2 mm. Pads were connected togetherin “string” using 0.5 oz Cu traces with 0.5 mil polyimide on the frontand back and between electrode pads providing insulation and isolation.The pads were then plated up so the finished pad height was abovepolyimide cover-lay. The 0.2 mm separation between connected pads wasimplemented to retain flexibility and to ensure the connection wasmaintained during flexing. An electroless nickel-immersion gold coatingwas used to cover all exposed copper for safety. These electrodes werethen adhered to the balloon using a flexible UV cured adhesive.

Referring now to FIG. 16, suitable power ranges for providing thedesired heating of the target tissue, and/or for limiting of heating tocollateral tissues, may depend at least in part on the time for whichenergy is applied, on the electrode (or other energy transmittingsurface) geometry, and the like. First, when applying the treatmentsdescribed herein to tissues with electrodes, there may be preferred aload impedance range of the tissues within the circuit so as to avoidhaving to apply voltages and/or currents that are outside desirableranges, particularly when applying powers within ranges describedherein. Suitable load impedance ranges would generally be within a rangefrom about 20 Ohms to about 4500 Ohms, more typically being in a rangefrom about 40 Ohms to about 2250 Ohms, and preferably being in a rangefrom about 50 to about 1000 Ohms.

The load impedance of the tissue within the circuit may depend on thecharacteristics of the tissue, and also (for example) on the geometry ofa bipolar pair of electrodes that engage the tissue, as the electrodesgeometries influence the geometry of the tissue effectively includedwithin the circuit. The tissue to which energy is directed may have aspecific conductivity in a range from about 0.2 Siemens per meter toabout 0.5 Siemens per meter. Different types of diseased tissues mayhave specific conductivities in different ranges, with some types ofdiseased tissues having specific conductivities in a range from about0.2 Siemens per meter to about 0.35 Siemens per meter, while others fallwithin a range from about 0.35 Siemens per to about 0.5 Siemens permeter. The spacing between the pair of electrodes and the length ofelectrodes (transverse to their spacing) will both have effects on theload impedance, with most embodiments having electrode pair spacings(adjacent edge-to-edge) of between 0.25 mm and 2.50 mm, exemplaryembodiments having electrode pair spacing of between 0.50 and 2.00 mm,and preferred embodiments having electrode pair spacing of between 0.75and 1.50 mm.

Regarding the length and spacing of the electrodes within a particularpair, these factors are inter-related with the power and impedance. Asthe length of the electrodes decreases, the impedance seen by thegenerator will go up, but the volume of tissue will go down, so that thepower setting on the generator may be decreased. As the gap between theelectrodes widens, the impedance seen by the generator will also go up,but the volume of tissue will go up as well, so that the power settingon the generator should be increased. Hence, there are roughly opposedeffects on load impedance when you decrease electrode length andelectrode spacing.

Desired power, energy, and time of the treatment are likewiseinter-related, and may also be at least related with electrode geometry.Speaking very generally, lower power treatments applied for long timestends to result in treatments with relatively higher total energies,while higher power treatments for shorter times tends to result in lowerenergy treatments. More specifically, at relatively low average power (1W or less) the total energy delivery per treatment may range from 8 to45 Joules. At higher power (more than 1 W), the total energy deliveryper treatment may range from 4 to 15 Joules. If the electrode spacingwere doubled, power may increase by four times. The power transmittedinto the tissue can be calibrated and scaled to the particular electrodeconfiguration, often in order to keep the power and energy density in adesirable range. Exemplary power ranges may be, for example from about 1to 5 Watts. The duration is longer for the lower power settings, andtypically varies from about 1 to 8 seconds. Very low power settings lessthan 1 Watt are also possible, using durations much longer than 10seconds.

It is also possible to scale the power settings significantly by varyingthe electrode configuration. If, for instance, the inner edge-to-edgespacing of the electrodes are increased, roughly 4 times the power maybe applied because the volume of tissue becomes roughly 4 times larger.As such, an electrode configuration that is somewhat different from theexemplary embodiments described herein could be used within a powerrange of roughly 4 to 20 Watts. Shortening the electrodes, and thusshortening and reducing the volume of the remodeling zones, would alsoaffect the magnitude of the power that is appropriate to apply to thetissue volume.

Referring still to FIG. 16, in order to quantify this complex set ofrelationships, and bound the space within which the exemplary treatmentdevice can operate, an empirical relationship between safe values ofseveral of these parameters may be generated and provided graphically,in table form, or by a mathematical relationships. An exemplary equationdescribing a particularly advantageous relationship is:

power=b*x̂2*L*(t̂(−0.59))

where b is a parameter in the range of 0.2 to 0.6, x is the inneredge-to-edge spacing of the electrodes in millimeters, L is the lengthof the electrodes in millimeters (and also the approximate length of theremodeling zone), the power is in Watts, and t is time in seconds. b hasunits of Watts/(mm̂3)*(secondŝ0.59). Exemplary treatments in the rangedescribed by this equation includes treatments such as 4 Watts for 2seconds, 3 Watts for 3 seconds, 2 Watts for 4 seconds, and 1 Watt for 12seconds with the exemplary electrode geometries described herein.Additionally, very low power long duration treatments such as 0.25 Wattsfor 180 seconds are covered as well. Alternative suitable treatmentrange falls within or near the set of curves shown in FIG. 16, whichshows approximate numbers for maximum power and time by electrodedimensions. Still further alternative treatment parameter values can beunderstood with reference to Table 2, which shows total energies fordifferent combinations of power and time for a few different electrodepair geometries.

TABLE 2 Alternative I Alternative II Exemplary Peripheral PeripheralTreatment Peripheral Treatment Exemplary Coronary Treatment CatheterCatheter Catheter Treatment Catheter X = 1 mm, X = 2 mm, X = 2 mm, X =0.5 mm, L = 16 mm Total L = 16 mm Total L = 8 mm Total L = 8 mm TotalTime Power Energy Time Power Energy Time Power Energy Time Power Energy(s) (W) (J) (s) (W) (J) (s) (W) (J) (s) (W) (J) 1 5 5 1 20 20 1 10 10 10.625 0.625 2 4 8 2 16 32 2 8 16 2 0.5 1 3 3 9 3 12 36 3 6 18 3 0.3751.125 4 2 8 4 8 32 4 4 16 4 0.25 1 12 1 12 12 4 48 12 2 24 12 0.125 1.530 0.5 15 30 2 60 30 1 30 30 0.0625 1.875 180 0.25 45 180 1 180 180 0.590 180 0.03125 5.625

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modification, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appending claims.

1. A system for inducing desirable temperature effects on a body tissuedisposed about a blood vessel, the system comprising: a catheter bodyhaving a proximal end and a distal end with an axis therebetween; aradially expandable member supported by the distal end of the catheterbody, the expandable member having a low profile insertion configurationand a larger profile configuration; and a plurality of electrodesdisposed about the expandable member so as to radially couple with awall of the blood vessel and define a plurality of remodeling zones inthe tissue when the expandable member is in the large profileconfiguration within the blood vessel, the electrodes configured totransmit a tissue remodeling energy between the electrodes and thetissue while inhibiting damage to the blood vessel.
 2. The system ofclaim 1, wherein the radially expandable member comprises a balloon,wherein the electrodes are mounted on a surface of the balloon arrangedin an array.
 3. The system of claim 2, wherein the electrodes arecircumferentially and axially offset.
 4. The system of claim 2, whereinthe plurality of electrodes are included in a plurality of separateflexible circuits distributed on the balloon.
 5. The system of claim 4,wherein each of the flexible circuits includes an associated bipolarelectrode pair.
 6. The system of claim 5, wherein the electrodes of eachbipolar electrode pair are disposed on a substrate of the associatedflexible circuit so as to have a predetermined bipolar pair separationdistance therebetween when the balloon is in the large profileconfiguration.
 7. The system of claim 6, wherein each electrodecomprises a plurality of pads, the pads electrically coupled together bya conductive trace, an insulation layer being disposed over the trace,and an electrode surface of the pads extending from the insulation layerso as to allow flexing along a length of the electrode.
 8. The system ofclaim 3 wherein the electrodes comprise a plurality of bipolar electrodepairs configured to be energized with RF energy, wherein the electrodesof the electrode pairs are circumferentially separated.
 9. The system ofclaim 8, wherein a circumferential distance between the electrodes ofthe electrode pairs is within a range from about 0.25 to 2.5 mm.
 10. Thesystem of claim 8, wherein a spacing between the electrodes of thebipolar electrode pairs is such that the remodeling zones betweenelectrodes of each pair, in combination, substantially circumscribe thecircumference of the balloon.
 11. The system of claim 8, wherein theelectrodes are configured so that the remodeling energy is applied at afrequency at which the body tissue is more conductive than collateraltissues.
 12. The system of claim 1 further comprising: a controllerelectrically coupling a power source to the plurality of electrodes forheating the remodeling zones with the energized electrodes so that atemperature of the tissue ranges from about 50° C. to about 90° C. 13.The system of claim 12, wherein the power source comprises an RFgenerator and the controller is configured to selectively direct RFenergy to electrode pairs of the plurality of electrodes.
 14. The systemof claim 12, wherein the controller is configured to use temperatureinformation of the tissue as feedback for delivering controlledtreatment energy to the electrodes.
 15. The system of claim 12, whereinthe controller is configured to energize the electrode pairs accordingto a duty cycle.
 16. The system of claim 12, wherein the controller isconfigured to energize the electrode pairs with about 0.25 to 20 Wattsaverage power for a duration between 1 to 180 seconds.
 17. The system ofclaim 12, wherein the controller is configured to energize the electrodepairs so as to deliver 8 to 45 Joules of energy in a treatment.
 18. Thesystem of claim 4 wherein an electrode length of each electrode isbetween 8 mm and 16 mm.
 19. The system of claim 1, wherein the system isconfigured to effect controlled delivery of remodeling energy using acharacteristic of the tissue measured with one or more electrode pairs.20. The system of claim 19, wherein the characteristic comprises a loadimpedance.
 21. A system for inducing desirable temperature effects on abody tissue disposed about a blood vessel, the system comprising: anintravascular catheter body having a proximal end and a distal end withan axis therebetween; an intravascular balloon supported by the distalend of the catheter body, the balloon having a low profile insertionconfiguration and a larger profile configuration; and a plurality offlex circuits distributed about the balloon, each flex circuit includinga pair of electrodes having a predetermined bipolar pair separationdistance therebetween; a power source configured to electrically couplewith the electrodes of the flex circuits, and to transmit a tissueremodeling energy between the electrodes of the pairs on the flexcircuits so as to provide an associated remodeling zone in the tissuefor each pair of electrodes when the balloon is inflated to the largeprofile configuration within the blood vessel.
 22. A method for inducingdesirable temperature effects on a desired body tissue disposed about abody lumen of a patient, the method comprising: positioning a radiallyexpandable member supported by a distal end of a catheter body withinthe lumen adjacent the desired tissue to be heated, the expandablemember having a low profile insertion configuration and a larger profileconfiguration; expanding the expandable member to the larger profileconfiguration within the lumen so as to engage a plurality of electrodesagainst a wall of the lumen, the plurality of electrodes defining aplurality of remodeling zones in the tissue; energizing the plurality ofelectrodes with a controller having a power source electrically coupledto the plurality of electrodes; and heating the remodeling zones in thetissue with the energized electrodes so as to induce desirabletemperature effects on the body tissue while inhibiting damage to thewall of the lumen.
 23. The method of claim 22, wherein the expandablemember comprises a balloon having the plurality of electrodes mounted onan outer surface thereof, and wherein expanding the expandable membercomprises inflating the balloon.
 24. The method of claim 22, wherein thebody lumen comprises a blood vessel, and the plurality of electrodescomprise a plurality of bipolar electrode pairs such that expanding theexpandable member urges one or more of the plurality of bipolarelectrode pairs against the vessel wall, and energizing the plurality ofelectrodes comprises delivering energy to the one or more bipolarelectrode when engaged against the vessel with an RF power source. 25.The method of claim 22, wherein the body lumen is an artery, and whereinheating with the energized electrodes is controlled so as to limitheating of an adventitial layer to below a deleterious responsethreshold.
 26. The method of claim 25, wherein heating is controlled byselectively firing bipolar electrode pairs of the plurality.
 27. Themethod of claim 26, wherein the bipolar electrode pairs are selectivelyfired according to a duty cycle.
 28. The method of claim 22, wherein theremodeling zones are circumferentially and axially offset.